Abstract: Speaking is one of the most complex actions that we perform, yet nearly all of us learn do it effortlessly. The ability to communicate through speech is often described as the unique and defining trait of human behavior. Despite its importance, the basic neural mechanisms that govern our ability to speak fluently remain unresolved. This proposal addresses two fundamental questions at the crossroads of linguistics, systems neuroscience, and biomedical engineering: 1) How are the coordinated movements of articulation functionally represented in human speech motor cortex? 2) Can we apply this new knowledge to decode speech motor cortex for the practical implementation of a neuro-prosthetic communication device? Our studies should greatly advance understanding of how the speech motor cortex encodes the precise control of articulation during speech production as well as determine whether this control system can be harnessed for novel rehabilitative strategies. Three potential areas of impact are: Neurobiology of Language, where results will shed light on neurophysiologic mechanisms of speech motor control;Human Neurophysiology, where insight gained may suggest novel methods for multivariate analysis of distributed population neural activity;and Translational NeuroEngineering, where results will apply directly to the development of a speech neuro-prosthetic device. We propose to investigate the functional organization of the speech motor cortex during consonant- vowel syllable production, and during articulatory compensation in the context of pertubation. Our methods utilizing safe, high-density, large-scale intracranial electrode recordings in humans represent a significant advancement over current noninvasive neuroimaging approaches. To accomplish this, we must innovate new, integrative approaches to speech motor control research. We will also employ novel and as of yet unproven analyses to 'read-out'speech motor cortex in real-time. Given that these ideas concerning the neural basis of speech production and its strategic application for neuroprosthetics are new and relatively untested, the level of risk in our proposal is substantially higher than in traditional investigator grants. The most debilitating aspect of profound paralysis due to trauma, stroke, or disease is loss of the ability to speak, which leads to profound social isolation. Our research focuses on novel methodologies gained in previous studies of speech perception in the human temporal lobe. We wish to broaden the impact of our research and innovate a related, and highly complementary field in the neurobiology of speech motor control. Public Health Relevance: Discovering the neural mechanisms of speech production has major implications for understanding a large number of communication disorders including mutism, stuttering, apraxia of speech, and aphasia. In addition, the proposed research seeks to translate critical knowledge on the neural control of speech to develop algorithms for a practical communication neuroprosthetic device to provide immediate, practical benefit to patients suffering from these disabling neurological conditions.